The Role of Sebaceous Gland Activity and Scalp Microoral

Metabolism in the Etiology of Seborrheic Dermatitis and Dandruff

Byung In Ro and Thomas L. Dawsonw

Department of Dermatology, College of Medicine, Chung Ang University, Seoul, Korea; wBeauty Care Technology Division, The Procter & Gamble Company,

Cincinnati, Ohio, USA

Most common scalp aking disorders show a strong correlation with sebaceous gland (SG) activity. Early SG
activity in the neonate results in microoral colonization and cradle cap. After maternal hormonal control subsides,
there is little SG activity until puberty, when the SG turns on under sex hormone control. When the SG activity
increases, the present but low Malassezia population has a new food source and proliferates, resulting in the scalp
itching and aking common to greater than 50% of adults. Dry scalp aking, dandruff, and seborrheic dermatitis are
chronic scalp manifestations of similar etiology differing only in severity. The common etiology is a convergence of
three factors: (1) SG secretions, (2) microoral metabolism, and (3) individual susceptibility. Dandruff and seborrheic dermatitis (D/SD) are more than supercial stratum corneum disorders, including alteration of the epidermis with hyperproliferation, excess lipids, interdigitation of the corneal envelope, and parakeratosis. The
pathogenic role of Malassezia in D/SD has recently been elucidated, and is focused on their lipid metabolism.
Malassezia restricta and M. globosa require lipids. They degrade sebum, free fatty acids from triglycerides, consume specific saturated fatty acids, and leave behind the unsaturates. Penetration of the modied sebaceous
secretions results in inammation, irritation, and scalp aking.

Key words: dandruff/microflora/sebaceous gland/seborrheic dermatitis/sebum

J Investig Dermatol Symp Proc 10:194 197, 2005

involved in development of epidermal structure and maintenance of the epidermal permeability barrier (Pilgram et al,
2001), carrying anti-oxidants to the skin surface (Theile et al,
1999), protection from microbial colonization, generation of
body odor, and pheromone generation (Kligman, 1963). It
has also recently come to light that sebum is directly involved in skin-specific hormonal signaling, epidermal differentiation, and protection of the skin from ultraviolet
irradiation (Thiboutot et al, 2003; Zouboulis, 2003).

Sebaceous Gland (SG) Activity

Human SG are found over the entire skin surface (except
the palms of the hands and soles of the feet), but sebum
secretion is highest on the scalp, face, chest, and back
(Strauss and Pochi, 1968a). Sebum is produced under hormonal control, with SG active at birth under the control of
maternal androgens. They quickly reduce in size and sebum
production until the onset of puberty. As puberty begins the
SG again activate, this time under the control of circulating
androgens. The sebum secretion rate increases throughout
the teens, remains steady through the 20s and 30s, then
lessens with age (Strauss et al, 1983; Dawber, 1997).
Throughout the active period of sebum secretion, the secretion rate is higher in males than in females. In males, the
rate remains higher longer, into the 50s and 60s, but in females, the secretion rate drops quickly after menopause
(Strauss and Pochi, 1968b). Common scalp flaking disorders all show a strong temporal correlation with sebaceous
activity, following the pattern of early cradle cap, low incidence until puberty, increasing incidence through the teens,
second and third decades, then declining (Dawber, 1997;
Gupta et al, 2003, 2004a, b).
The primary functions of sebum have historically been
controversial, but are recently being elucidated. Sebum is

Composition of Human Sebum

When secreted human sebum is a complex mixture of triglycerides, fatty acids, wax esters, sterol esters, cholesterol, cholesterol esters, and squalene (Fig 1) (Strauss et al,
1983). As the sebum is secreted, it consists primarily of
triglycerides and esters, which are broken down by commensal microbes into diglycerides, monoglycerides, and
the constituent free fatty acids. Human sebum contains
both saturated and unsaturated fatty acids, with a preponderance of unsaturates. The fatty acid chain lengths of human sebum vary considerably, but are predominantly 16
and 18 carbons (stearic, C18:0, oleic, C18:1D9, linoleic,
C18:2D9D12, palmitic, 16:0, sapienic, 16:1D6, and palmitoleic, C16:1D9, Fig 1). The role of specific fatty acids of
human sebum becomes apparent when we examine the
metabolism of Malassezia.

Abbreviations: D/SD, dandruff and seborrheic dermatitis; SG,

sebaceous gland

Copyright r 2005 by The Society for Investigative Dermatology, Inc.

194

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SEBACEOUS AND MICROFLORAL ACTIVITY IN SCALP DISEASE

195

Figure 1
Relative composition of human sebum. Samples of human sebum were collected and analyzed by gas chromatography. Peaks were identified by
comparison to known standards. Identifications confirmed by GC-mass spectrometry.

Figure 2
Triglyceride degradation and increased free fatty acids after incubation of artificial sebum by Malassezia globosa. Lipid composition
analyzed as in Fig. 1, but following incubation of M. globosa for 24 hours with defined lipid matrix.

196 RO AND DAWSON

JID SYMPOSIUM PROCEEDINGS

60%

High Acid (Active Malassezia)

Low Acid (no Malassezia)

50%

Figure 3
Triglyceride and fatty acid composition of sebum extracted from human
scalp. Lipid profile analyzed as in Fig.
1, samples collected from a dandruff
sufferer with high Malassezia counts
before (red, primarily free fatty acids) or
after (blue, both triglycerides and free
fatty acids) treatment with a commercial antifungal shampoo.

40%

30%

20%

10%

0%
1

10 11

12 13 14 15

Role of Malassezia

16 17 18 19

20 21 22

Over 100 y ago, Malassez implicated the yeast Pityrosporum in the etiology of dandruff (Malassez, 1874). Although
there has been much debate regarding whether the yeast is
actually a causative agent (Leyden et al, 1976; Shuster,
1984) there is now general agreement (Pierard Franchimont
et al, 2000; Gupta and Kohil, 2004).
Early SG activity in the neonate allows initial Malassezia
colonization and is likely an initiating factor for cradle cap. The
Malassezia population then drops dramatically, only to re-appear as SG activity increases at the onset of puberty (Gupta
and Kohil, 2004). As the SG begins increased activity, the
present but low Malassezia population has a new food source
and proliferates (Gupta et al, 2001; Gupta and Kohil, 2004).
Malassezia, however, have a very specific taste for individual
fatty acids (Gueho et al, 1996, 1998). The Malassezia lipases
are non-specific and degrade any available triglycerides (Fig
2). The saturated fatty acids are consumed, and the abundant
unsaturates are left on the skin (Figs 2 and 3).
Recently, novel molecular methods have overcome the
difficulties presented by culture of Malassezia, and the specific Malassezia species present on human scalp have been
elucidated (Gupta et al, 2000; Gaitanis et al, 2002; Gemmer
et al, 2002; Sugita and Nishikawa, 2003; Sugita et al, 2003).
Malassezia nomenclature has evolved over the last century,
but the genus now consists of 10 distinct species: M. globosa, M. restricta, M. furfur, M. sympodialis, M. slooffiae, M.
obtusa, M. nana, M. dermatis, M. japonica, and the sole
non-lipid-dependent species, M. pachydermatis. All except
M. pachydermatis can be found on human skin, but the
most common species on human scalp are M. restricta
and M. globosa (Gemmer et al, 2002). Further molecular
investigation will undoubtedly produce more distinct genetic entities, but detailed biochemical and physiological experiments will be needed to define the actual species.

is visibly excessive scalp scaling. Seborrheic dermatitis is a

more severe disorder which can include increased desquamation of facial areas other than the scalp and visible inflammation. Although dandruff is not a life-threatening
disease, its presence can lead to loss of self-esteem and
a negative social image (Hay and Graham-Brown, 1997).
D/SD are characterized by itching and visible dry or oily
flakes, induced by excess turnover of scalp cells (Dawber,
1997). D/SD are more than just superficial disorders of the
stratum corneum, including alteration of the epidermis with
hyperproliferation, excess intercellular and intracellular lipids, interdigitation of the corneal envelope, and parakeratosis (McOsker and Hannon, 1967; Warner et al, 2001).
Although Malassezia are not numerically correlated to D/
SD, recent evidence strongly supports their causal role
(Gupta and Kohil, 2004). This evidence includes the effectiveness of multiple chemical entities whose sole common
mechanism of action is antifungal activity, as well as the
very distinct numerical correlation of reduction in severity
with reduction of Malassezia numbers (Shuster, 1984).
Combination of several recent lines of investigation points
out a novel mechanism for the etiology of D/SD. M. restrica
and M. globosa require lipids as food source (Guillot and
Gueho, 1995; Gueho et al, 1996; Guillot et al, 1996), and are
perfectly adapted for life on the human scalp. The Malassezia degrade sebum, freeing multiple fatty acids from
triglycerides (Fig 2). They consume the very specific saturated fatty acids necessary for their proliferation, leaving
behind the unsaturated fatty acids (Fig 3). Experimentally, it
can be shown that the changes in sebum composition over
time are a direct result of Malassezia metabolism. Table I
illustrates the effect of removing scalp microflora with an
antimicrobial shampoo (removal of microorganisms verified
by molecular analysis, data not shown). The sebum composition changes back to near normal levels of triglyercides
and free fatty acids.

Etiologic Mechanism of Dandruff and

Seborrheic Dermatitis (D/SD)

Individual Susceptibility

D/SD are chronic clinical scalp conditions affecting greater

than 50% of the population, the primary symptom of which

Penetration of the modified sebaceous secretions into the

stratum corneum breaks down the skin barrier function, re-

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SEBACEOUS AND MICROFLORAL ACTIVITY IN SCALP DISEASE

Table I. Relative composition of human sebum

As secreted
(%)

Post Malassezia
exposure
(%)

Post antifungal
treatment
(%)

Triglycerides

435

18

32

Free fatty acids

o13

32

16

Wax esters

25

23

25

Squalene

15

15

15

Cholesterol

Cholesterol esters

5

5

5

Others

sulting in inflammation, irritation, and the resultant scalp

flaking. Recent data shows that the penetration and inflammation response to the fatty acids are different between
dandruff and non-dandruff sufferers.1
Additionally, immunodeficiency, such as AIDS, allows
excess Malassezia proliferation, resulting in severe D/SD.
Physical factors, nutritional disorders, drugs, and neurotransmitter abnormalities are additional aggravating factors.

Conclusion
The common etiology of D/SD is therefore a convergence of
three factors: (1) SG secretions, which provide the substrate
for Malassezia growth; (2) Malassezia metabolism of the
sebaceous secretions, releasing irritating unsaturated fatty
acids; and (3) individual susceptibility to the penetration of
the fatty acids and the resultant inflammation.
The authors would like to thank Christina Gemmer, Yvonne DeAngelis,
and Meredith Leland for their expertise in handling, growing, and
detecting Malassezia; Shane Whitaker and Joe Kaczvinsky for their
analytic expertise; and Aditya Gupta and Teun Boekhout for their expertise in Malassezia clinical implications and phylogeny/physiology,
respectively.
DOI: 10.1111/j.1087-0024.2005.10104.x
Manuscript received September 20, 2004; accepted for publication
October 21, 2004
Address correspondence to: Thomas L. Dawson Jr, 11810 East Miami
River Road, Cincinnati, Ohio, 45252, USA. Email: Dawson.tl@pg.com

References
Dawber R: Diseases of the Hair and Scalp. London: Blackwell Science, p 499
504, 1997
Gaitanis G, Velegraki A, Frangoulis E, et al: Identification of Malassezia species
from patient skin scales by PCR-RFLP. Clin Microbiol Infect 8:162173,
2002
Gemmer CM, DeAngelis YM, Theelen B, Boekhout T, Dawson TL: Fast, noninvasive method for molecular detection and differentiation of Malassezia
yeast species on human skin and application for the method to dandruff
microbiology. J Clin Microbiol 40:33503357, 2002

1
DeAngelis Y, Leland M, Gemmer C, et al: The three etiologic
facets of dandruff and seborrheic dermatitis: Malassezia fungi, sebaceous lipids, and individual sensitivity. Intercontinental Meeting
of Hair Research Societies, Conference poster, 2004.

197

Gueho E, Boekhout T, Ashbee HR, Guillot J, Van Belkum A, Faergemann J: The

role of Malassezia species in the ecology of human skin and as pathogens. Med Mycol 36 (Suppl):220229, 1998
Gueho E, Midgley G, Guillot J: The genus Malassezia with description of four new
species. Antonie Van Leeuwenhoek 69:337355, 1996
Guillot J, Gueho E: The diversity of Malassezia yeasts confirmed by rRNA sequence and nuclear DNA comparisons. Antonie van Leeuwenhoek
67:297314, 1995
Guillot J, Gueho E, Lesourd M, Midgley G, Chevrier B, Dupont B: Identification of
Malassezia species. J Mycol Med 6:103110, 1996
Gupta AK, Kohli Y, Summerbell RC: Molecular differentiation of seven Malassezia
species. J Clin Microbiol 38:18691875, 2000
Gupta AK, Batra R, Bluhm R, Boekhout T, Dawson TL: Skin diseases associated
with Malassezia species. J Am Acad Dermatol 51:785798, 2004a
Gupta AK, Bluhm R, Cooper EA, Summerbell RC, Batra R: Seborrheic dermatitis.
Dermatol Clin 21:401412, 2003
Gupta AK, Kohli Y: Prevalence of Malassezia species on various body sites in
clinically healthy subjects representing different age groups. Med Mycol
42:3542, 2004
Gupta AK, Kohli Y, Summerbell RC, Faergemann J: Quantitative culture of Malassezia species from different body sites of individuals with or without
dermatoses. Med Mycol 39:243251, 2001
Gupta AK, Madzia SE, Batra R: Etiology and management of seborrheic dermatitis. Dermatology 208:8993, 2004b
Hay RJ, Graham-Brown RA: Dandruff and seborrhoeic dermatitis: Causes and
management. Clin Exp Dermatol 22:36, 1997
Kligman AM: The uses of sebum? In: Montagne W, Ellia RA, Silver AF (eds).
Advances in Biology of the Skin, Vol. 4, The Sebaceous Glands. Oxford:
Pergamon Press, 1963; p 110124
Leyden JJ, McGinley KJ, Kligman AM: Role of microorganisms in dandruff. Arch
Dermatol 112:333338, 1976
Malassez L: Note Sur le Champignon du Pityriasis Simple. Arch Physiol 1:451
459, 1874
McOsker DE, Hannon DP: Ultrstructural studies of dandruff-involved scalp tissue.
Toilet Goods Assoc 47:58, 1967
Pierard-Franchimont C, Hermanns JF, Degreef H, Pierard GE: From axioms to
new insights into dandruff. Dermatology 200:9398, 2000
Pilgram GS, Meulen J, van der Gooris GS, Koerten HK, Bouwstra JA: The influence of two azones and sebaceous lipids on the lateral organization of
lipids isolated from human stratum corneum. Biochim Biophys Acta
1511:244254, 2001
Shuster S: The aetiology of dandruff and the mode of action of therapeutic
agents. Br J Dermatol 111:235242, 1984
Strauss JS, Downing DT, Ebling FJ: Sebaceous glands. In: Goldsmith LA (eds).
Biochemistry and Physiology of Skin. New York: Oxford University Press,
p 569595, 1983
Strauss JS, Pochi PE: Histology, histochemistry, and electron microscopy of sebaceous glands in man. In: Gans O, Steigleder GK (eds). Handbuch der
Haut-und Geschlechtskrankheiten; Normale und Pathologische Anatomie
der Haut I. Berlin: Springer-Verlag, 1968a; p 184223
Strauss JS, Pochi PE: The change of human sebaceous gland activity with age.
In: Baccareda-Boy A, Morretti G, Frey JR (eds). Biopathology of Pattern
Alopecia. Basel: Karger, 1968b; p 166
Sugita T, Kodama M, Saito M, Ito T, Kato Y, Tsuboi R, Nishikawa A: Sequence
Diversity of the intergenic spacer region of the rRNA gene of Malassezia
globosa colonizing the skin of patients with atopic dermatitis and healthy
individuals. J Clin Microbiol 41:30223027, 2003
Sugita T, Nishikawa A: Molecular and quantitative analysis of Malassezia microflora on the skin of atopic dermatitis patients and genotyping of M. globosa DNA. Jpn J Med Mycol 44:6164, 2003
Theile JJ, Weber SU, Packer L: Sebaceous gland activity is a major physiologic route
of vitamin E delivery to the skin. J Invest Dermatol 113:10061010, 1999
Thiboutot D, Jabara S, McAllister JM, Sivarajah A, Gilliland K, Cong Z, Clawson
G: Human skin is a steroidogenic tissue: Steroidogenic enzymes and
cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1). J Invest Dermatol 120:905914, 2003
Warner RR, Schwartz JR, Boissy Y, Dawson TL: Dandruff has an altered stratum
corneum ultrastructure that is improved with zinc pyrithione shampoo. J
Am Acad Dermatol 45:897903, 2001
Zouboulis CC: Sebaceous gland in human skinthe fantastic future of a skin
appendage. J Invest Dermatol 120:xivxv, 2003